VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage
VRK1 interacts with p53 forming a basal complex that is activated by UV-induced DNA damage
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DOI：
10.1016/j.febslet.2014.01.040
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发表时间：
2014-03-03
期刊：
影响因子：
3.5
通讯作者：
Lazo, Pedro A.
中科院分区：
文献类型：
--
作者：
Lopez-Sanchez, Inmaculada;Valbuena, Alberto;Lazo, Pedro A.
DNA损伤的即刻细胞反应需要通过激酶激活P53。我们发现P53与VRK1形成一个基本稳定的复合体，VRK1是一种Ser-Thr激酶，通过特异性磷酸化P53来响应紫外线诱导的DNA损伤。这种相互作用是通过P53 DNA结合域进行的，频繁的P53 DNA接触突变，如R273H、R248H或R280K，不会破坏复合体。紫外线诱导的DNA损伤激活VRK1，并伴随着Thr-18处P53的磷酸化，然后积累。我们认为VRK1-P53基础复合体是细胞对DNA损伤的即时反应的早期预警系统。(C)2014年欧洲生化学会联合会。爱思唯尔出版，版权所有。
DNA damage immediate cellular response requires the activation of p53 by kinases. We found that p53 forms a basal stable complex with VRK1, a Ser-Thr kinase that responds to UV-induced DNA damage by specifically phosphorylating p53. This interaction takes place through the p53 DNA binding domain, and frequent DNA-contact mutants of p53, such as R273H, R248H or R280K, do not disrupt the complex. UV-induced DNA damage activates VRK1, and is accompanied by phosphorylation of p53 at Thr-18 before it accumulates. We propose that the VRK1-p53 basal complex is an early-warning system for immediate cellular responses to DNA damage. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.